Increase In Sodium Permeability Research Articles

A REVIEW ON PYRETHROID AS INSECTIDE AND IT’S ADVERSE EFFECT ON HUMAN

Synthetic pyrethroids are insecticide as well as pesticide made from naturally occurring pyrethrins found in dried Chrysanthemum flowers' pyrethrum. In present review use of pyrethroid as insecticide and its harmful effects on human beings are focused. Pyrethroids Modifying the kinetics of voltage-sensitive sodium channels, which mediate the nerve membrane's temporary increase in sodium permeability that underpins the nerve action potential, has an effect on insect nerves, with is benefits it also shows adverse effect on human health if its consumption is high it can cause damage to sperm DNA, respiratory disorder, circulatory disease and many more.

Sodium permeable and "hypersensitive" TREK-1 channels cause ventricular tachycardia.

In a patient with right ventricular outflow tract (RVOT) tachycardia, we identified a heterozygous point mutation in the selectivity filter of the stretch‐activated K2P potassium channel TREK‐1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK‐1. In addition, mutant channels exhibit a hypersensitivity to stretch‐activation, suggesting that the selectivity filter is directly involved in stretch‐induced activation and desensitization. Increased sodium permeability and stretch‐sensitivity of mutant TREK‐1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT. We present a pharmacological strategy to rescue the selectivity defect of the TREK‐1 pore. Our findings provide important insights for future studies of K2P channel stretch‐activation and the role of TREK‐1 in mechano‐electrical feedback in the heart.

Being positive: revisiting the elevated sodium permeability hypothesis in cystic fibrosis

Being positive: revisiting the elevated sodium permeability hypothesis in cystic fibrosis

Structure and Function of the Voltage Sensor of Sodium Channels Probed by a β-Scorpion Toxin

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor site 4 and induce a negative shift in the voltage dependence of activation through a voltage sensor-trapping mechanism. Kinetic analysis showed that beta-scorpion toxin binds to the resting state, and subsequently the bound toxin traps the voltage sensor in the activated state in a voltage-dependent but concentration-independent manner. The rate of voltage sensor trapping can be fit by a two-step model, in which the first step is voltage-dependent and correlates with the outward gating movement of the IIS4 segment, whereas the second step is voltage-independent and results in shifted voltage dependence of activation of the channel. Mutations of Glu(779) in extracellular loop IIS1-S2 and both Glu(837) and Leu(840) in extracellular loop IIS3-S4 reduce the binding affinity of beta-scorpion toxin. Mutations of positively charged and hydrophobic amino acid residues in the IIS4 segment do not affect beta-scorpion toxin binding but alter voltage dependence of activation and enhance beta-scorpion toxin action. Structural modeling with the Rosetta algorithm yielded a three-dimensional model of the toxin-receptor complex with the IIS4 voltage sensor at the extracellular surface. Our results provide mechanistic and structural insight into the voltage sensor-trapping mode of scorpion toxin action, define the position of the voltage sensor in the resting state of the sodium channel, and favor voltage-sensing models in which the S4 segment spans the membrane in both resting and activated states.

Dramatic Magnesium Efflux Induced by High Potassium in Rat Thymocytes

When incubated in 150 mM KCl, rat thymocytes exhibited a very important magnesium efflux (11.4 ± 0.7 mmoles/liter cells/20 min, n = 29), about 90 times higher than the physiological magnesium efflux catalyzed by the Na-Mg exchanger (0.126 ± 0.093 mmoles/liter cells/20 min). Cells remained viable (trypan blue test) and membrane integrity was shown by the absence of an increase in sodium permeability. K+-induced magnesium efflux exhibited the following properties: (i) it required the presence of external chloride; (ii) it was fully blocked by DIOA, a selective KCl-cotransporter inhibitor (IC50 = 35 μm); and (iii) it was associated to a progressive increase in cell volume via the DIOA-sensitive K-Cl cotransporter. Such cell swelling seems to play a causal role, because (i) hypertonic media (+400 mM sucrose) abolished K+-induced magnesium efflux and (ii) hypotonic Ringer media (205 mOsm) increased both cell volume and magnesium efflux (from a basal value of 0.35 ± 0.03 mmoles/liter cells/20 min up to 1.44 ± 0.24 mmoles/liter cells/20 min), even in the presence of DIOA. In conclusion, high potassium induced a dramatic release of intracellular magnesium from rat thymocytes. Such a phenomenon was, at least in part, caused by cell swelling via the DIOA-sensitive K-Cl cotransporter. The nature of the magnesium transport mechanism and its role in the transduction signal of K-Cl cotransporter activation by cell swelling deserve further investigation.

Stimulation of active sodium-potassium transport by hydrogen peroxide in cultured rabbit nonpigmented ciliary epithelium

Purpose. Studies were conducted to examine the effect of hydrogen peroxide on active sodium-potassium transport in a cell line derived from nonpigmented ciliary epithelium of the rabbit eye. Methods. Studies were carried out using a rabbit nonpigmented ciliary epithelium cell line. 86 Rb uptake by intact cells was measured in the presence or absence of ouabain. The ouabain-sensitive potassium (86 Rb) uptake rate was used as an index of the rate of active sodium-potassium transport. Cell sodium content was measured by atomic absorption spectrophotometry. Na,K-ATPase activity was determined by measuring ATP hydrolysis in the presence or absence of ouabain, using membrane material isolated by centrifugation of cell homogenates. Results. Ouabain-sensitive potassium (86 Rb) uptake rate measured in cells that had been preincubated with 200µM hydrogen peroxide for either 30 min or 60 min was increased to 196% and 181% of the control uptake rate, respectively. Lesser concentrations of hydrogen peroxide caused lesser degrees of stimulation. 200µM hydrogen peroxide caused an increase of cell sodium content. Such a change of cell sodium content is likely to be responsible, at least in part, for the observed stimulation of active sodium-potassium transport. However, the response may also be partly dependent on activation of a protein kinase since the serine/threonine protein kinase inhibitors staurosporine (1µM) and H-89 (20µM) were both found to prevent the stimulatory effect of 200µM hydrogen peroxide on ouabain-sensitive potassium (86 Rb) uptake. Interestingly, neither H-89 nor staurosporine prevented the elevation of sodium content in cells that received 200µM hydrogen peroxide. Conclusions. Taken together, these findings suggest a low concentration of hydrogen peroxide causes increased sodium entry into the cell and also activates a protein kinase-dependent mechanism for sodium pump stimulation. The protein kinase-dependent mechanism does not appear to be triggered by an increased rate of sodium entry since staurosporine did not prevent the stimulation of ouabain-sensitive potassium (86 Rb) uptake elicited by an increase in sodium permeability caused by amphotericin B.

Disruption of Cell Volume Regulation by Mercuric Chloride Is Mediated by an Increase in Sodium Permeability and Inhibition of an Osmolyte Channel in Skate Hepatocytes

The mechanism by which mercury leads to cell swelling and impairs the normal regulatory volume decrease (RVD) in cells swollen in hypotonic media was examined in hepatocytes isolated from the little skate,Raja erinacea,an osmoconforming marine elasmobranch. Skate hepatocytes treated with 50 μMHgCl2in isotonic medium swelled to volumes double those of control cells, and this was associated with an increase in Na+and K+permeability. The gain in intracellular Na+exceeded the K+loss by 0.27 μEq/mg protein, accounting in large part for the observed cell swelling. The effects of mercury were blunted when hepatocytes were incubated in medium in which the Na+was replaced with K+, and were essentially absent when Na+was replaced with choline+, indicating an important role of Na+influx in mediating mercury's effects on cell volume regulation. The inhibition of RVD by mercury was prevented if the metal was administered as a mercaptide with dithiothreitol or glutathione. However, when these chelating agents were added after the mercury, only the membrane permeant dithiothreitol was able to reverse the inhibition of RVD, suggesting an intracellular site of action. Mercuric chloride also produced a concentration-dependent inhibition of the ATP-sensitive volume-regulatory osmolyte channel in skate hepatocytes, as assessed by inhibition of swelling-activated [14C]taurine efflux. [14C]Taurine efflux was inhibited at mercury concentrations (20–40 μM) that had no effect on intracellular ATP levels or ATP/ADP ratios, consistent with a direct interaction with the channel. These findings indicate that mercury impairs cell volume regulation in skate hepatocytes at multiple sites, including the volume-regulatory osmolyte channels, and Na+and K+permeability pathways. The combined effects of increased Na+influx and the inability to extrude organic osmolytes may account for the inhibition of RVD.

Cytogenetic and molecular localization of tipE: a gene affecting sodium channels in Drosophila melanogaster.

Voltage-sensitive sodium channels play a key role in nerve cells where they are responsible for the increase in sodium permeability during the rising phase of action potentials. In Drosophila melanogaster a subset of temperature-sensitive paralytic mutations affect sodium channel function. One such mutation is temperature-induced paralysis locus E (tipE), which has been shown by electrophysiology and ligand binding studies to reduce sodium channel numbers. Three new gamma-ray-induced tipE alleles associated with either visible deletions in 64AB or a translocation breakpoint within 64B2 provide landmarks for positional cloning of tipE. Beginning with the flanking cloned gene Ras2, a 140-kb walk across the translocation breakpoint was completed. Germline transformation using a 42-kb cosmid clone and successively smaller subclones localized the tipE gene within a 7.4-kb genomic DNA segment. Although this chromosome region is rich in transcripts, only three overlapping mRNAs (5.4, 4.4, and 1.7 kb) lie completely within the smallest rescuing construct. The small sizes of the rescuing construct and transcripts suggest that tipE does not encode a standard sodium channel alpha-subunit with four homologous repeats. Sequencing these transcripts will elucidate the role of the tipE gene product in sodium channel functional regulation.

A Putative ATP-Activated Na + Channel Involved in Sperm-Induced Fertilization

Extracellular application of adenosine triphosphate (ATP) to defolliculated Xenopus laevis oocytes activated a saturating inward current with a maximal amplitude E(max) of 2.4 +/- 0.2 microamperes and an apparent Michaelis constant of 197.6 micromolar. The current was carried predominantly by sodium ions and potently inhibited by amiloride, guanosine triphosphate (GTP), and its nonhydrolyzable analogs guanosine 5'-[beta,gamma-imido]triphosphate (GppNHp) and guanosine 5'-O-(3-thiotriphosphate). Likewise, in vitro fertilization using mature eggs and Xenopus sperm was inhibited by amiloride, GTP, and GppNHp. Hence, an ATP receptor on the egg membrane may be the recipient target for ATP originating in sperm, suggesting that an ATP-induced increase in sodium permeability mediates the initial sperm to egg signal in the fertilization process.

Multiple Serotonin-Activated Currents in Isolated, Neuronal Somata from Locust Thoracic Ganglia

ABSTRACT Three different responses were evoked by pressure micro-application of serotonin onto freshly dissociated, current- and voltage-clamped neuronal somata from the thoracic ganglia of the locust Locusta migratoria. In some neurones, an inward current, I(5HT)K, resulting from a decrease in potassium conductance, with slow kinetics and maximum activation at membrane potentials of –60 to –70 mV, was evoked by serotonin and by the 5-HT3 agonist 2-methyl serotonin. This current was completely abolished by either 10 mmol l-1 caesium or 5 mmol I-1 rubidium and partially blocked by 50mmoll-1 tetraethylammonium or 5 mmol l-1 4-aminopyridine. The response was antagonised by the 5-HT2-specific compounds, ketanserin and ritanserin. In other somata, serotonin, 2-methyl serotonin and the 5-HT3 antagonist ICS 205 930 evoked a second current, I(5HT)Na, which was due to an increase in sodium permeability and had slow kinetics similar to that of I(5HT)K. This current was inward over the membrane potential range –30 to –80 mV and increased with hyperpolarisation. The response was blocked by sodium-free saline and the 5-HT3 receptor antagonist MDL 72222. In other neurones, at membrane potentials more positive than –50 mV, serotonin pulses could activate a third current, I(5HT)X, which increased with depolarisation of the membrane potential and had comparatively fast kinetics. Activation of the current was accompanied by a decrease in membrane conductance. This response was completely blocked by 4-aminopyridine and weakly inhibited by both caesium and tetraethylammonium and is, therefore, probably a potassium current. The three currents described here differ in their pharmacology, their ionic mechanisms and their dependence on membrane potential from the serotonin-activated currents reported for vertebrates and they provide evidence for the mechanism of action of serotonin as a neurotransmitter in insects.

Diacylglycerol activation of protein kinase C results in a dual effect on Na+,K(+)-ATPase activity from intact renal proximal tubule cells.

This study evaluated the effect of L-1-oleoyl-2-acetyl-sn-3-glycerol (OAG) on ouabain-sensitive Na,K-dependent oxygen consumption (Na,K-QO2) in intact renal proximal tubule cells (RPTC). Basal Na,K-QO2 (nmol O2/mg protein per min) was 20.0 +/- 1.0. Incubation with 10 nM of OAG induced a dual effect on Na,K-QO2, with an initial stimulation (maximal at 10 min, 37.1 +/- 5.0), followed by an inhibition (significant at 20 min, 16.3 +/- 1.0). No changes in ouabain-insensitive QO2 were observed in any of the protocols. The effects were abolished by sphingosine, a protein kinase C inhibitor. Stimulation was abolished by amiloride 0.1 mM. Amiloride had no effect on Na,K-QO2 at the concentration used. Stimulation was not potentiated by the sodium ionophore, amphotericin B, and the later inhibition was still observed in the presence of amphotericin B. The initial stimulation was attributed to an increase in sodium permeability, while the later inhibition was attributed to a direct effect on the Na,K-pump. Regulation of Na+,K(+)-ATPase activity by protein kinase C in intact RPTC can be accomplished by a direct effect on the protein or as a secondary effect consequent upon changes in intracellular sodium.

Structure and Modulation of Voltage‐Gated Ion Channels

The depolarizing phase of the action potential in most excitable cells results from an initial increase in sodium permeability mediated by voltage-gated sodium channels followed by a more prolonged increase in calcium permeability mediated by voltage-gated calcium channels. Repolarization is then caused by activation of voltage-gated potassium channels. Calcium entering the cell during the action potential serves as an intracellular messenger to initiate secretion, contraction, and metabolic and regulatory events. The voltage-gated ion channels are also subject to regulation by interaction with G proteins and by protein phosphorylation stimulated by intracellular second messengers. This form of ion channel modulation has been reported for many calcium channels and potassium channels, but has been described less frequently for sodium channels. In this brief chapter, we have reviewed research from our laboratory which has given new insight into the molecular properties of sodium channels and the molecular basis oftheir modulation by cAMP-dependent protein kinase and protein kinase C.

Digitalislike circulating factor in hypertension: Potential messenger between salt balance and intracellular sodium

Sodium chloride has no clearly established local direct action on blood vessels to produce constriction; on the contrary, it has an immediate local indirect action via osmolality, which produces vasodilation. Thus in order to explain salt-induced hypertension, a delayed remote indirect vasoconstrictor action must be postulated. This indirect vasoconstrictor action is apparently the result of volume expansion. Acute volume expansion imparts three physiologic properties to the plasma; these are the ability to inhibit Na,K-ATPase and the Na-K pump, to cause natriuresis, and to sensitize blood vessels to vasoconstrictor agents. Similarly, low-renin, volume-expanded hypertension endows the plasma with the capacity to inhibit the Na,K-ATPase pump, to sensitize blood vessels to vasoconstrictor agents, and to raise blood pressure. These properties apparently result from a circulating digitalislike substance(s), perhaps derived from the hypothalamus and/or adrenals. We here review the considerable effort expended in identifying the agent or agents, and conclude that both steroidal and peptidic structure must be considered. Regardless of its structure, we hypothesize that when sodium excretion does not keep pace with sodium intake, its release leads to increased contractile activity of cardiac and vascular smooth muscle and hence hypertension. Inhibition of the Na-K pump increases the intracellular sodium concentration, particularly when superimposed on genetic- or aldosterone-induced increased sodium permeability, resulting in depolarization and increased calcium influx (vascular smooth muscle) or altered Na(+)-Ca2+ exchange and decreased calcium efflux (heart muscle). The increased intracellular calcium concentration then accounts for the increased contractile activity. Depolarization may also increase the sensitivity of vascular smooth muscle to vasoconstrictor agents such as norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic agents for the [formula omitted] detection of vascular sodium transport defects in hypertension

Anatagonists to angiotensin, catecholamines, aldosterone, and vasopressin have long been used to help determine agonist roles in hypertension. We here call attention to a possible extension of this approach to detect, evaluate, and treat vascular sodium transport defects in hypertension. Two basic types of transport defects have been identified in the blood vessels of hypertensive animals, increased sodium permeability and decreased sodium pump activity. Intravenous injection of 6-iodo-amiloride, a sodium channel blocker and vasodilator, produces an immediate and sustained decrease in blood pressure in two genetic models of hypertension characterized by increased permeability of the vascular smooth muscle cell membrane to sodium (Okamoto spontaneously hypertensive rat, Dahl salt sensitive rat), whereas it produces only a transient fall in arterial pressure in two renal models of hypertension having normal sodium permeability in vascular smooth muscle cells (reduced renal mass-saline rat, one-kidney, one clip rat). Canrenone, a metabolic product of spironolactone which can compete with ouabain for binding to Na +,K +-ATPase at the digitalis receptor site, decreases blood pressure in a low renin, volume expanded model of hypertension which has been shown to have depressed sodium pump activity in arteries and increased sodium pump inhibitor in plasma (reduced renal mass-saline rat) but has no effect on blood pressure in a genetic model of hypertension which has been shown to have increased sodium pump activity secondary to increased sodium permeability (spontaneously hypertensive rat). Thus, a sodium channel blocker and a competitor to ouabain binding can detect and determine the functional significance of sodium transport defects in the blood vessels of intact hypertensive animals. Studies in red and white blood cells suggest that similar defects may exist in the blood vessels of hypertensive humans. Thus, this approach, probing for vascular transport defects in the intact animal, may ultimately also be useful in the clinical setting.

Increased sodium permeability and transport as primary events in the hypertensive response to deoxycorticosterone acetate (DOCA) in the rat.

We report here that 18-24 h after subcutaneous administration of DOCA to the rat, plasma [Na] was significantly increased and [K] reduced without change in cell Na concentration, [Na]i, or cell K concentration, [K]i, as measured in rapidly excised tail arteries. The large increase in the transmembrane K gradient, operationally [K]i/[K]o, was associated with a significant decline of about 7 mV in the transmembrane membrane potential (Em) measured in small mesenteric arteries in situ, and a small but significant rise in blood pressure. We conclude that the permeability of the membrane to Na relative to K was increased at this time but enhanced transport of both ions was sufficient to maintain near-normal cell concentrations. These were primary events in relation to the hypertension induced by DOCA, as the rise in plasma [Na] and fall in [K] were already apparent at 6 h.

Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity.

Intestinal absorptive cells may modulate both the structure and function of occluding junctions by a cytoskeleton dependent mechanism (Madara, J. L., 1983, J. Cell Biol., 97:125-136). To further examine the putative relationship between absorptive cell occluding junctions and the cytoskeleton, we assessed the effects of cytochalasin D (CD) on occluding junction function and structure in guinea pig ileum using ultrastructural and Ussing chamber techniques. Maximal decrements in transepithelial resistance and junctional charge selectivity were obtained with 10 micrograms/ml CD and the dose-response curves for these two functional parameters were highly similar. Analysis of simultaneous flux studies of sodium and the nonabsorbable extracellular tracer mannitol suggested that CD opened a transjunctional shunt and that this shunt could fully account for the increase in sodium permeability and thus the decrease in resistance. Structural studies including electron microscopy of detergent-extracted cytoskeletal preparations revealed that 10 micrograms/ml CD produced condensation of filamentous elements of the peri-junctional contractile ring and that this was associated with brush border contraction as assessed by scanning electron microscopy. Quantitative freeze-fracture studies revealed marked aberrations in absorptive cell occluding junction structure including diminished strand number, reduced strand-strand cross-linking, and failure of strands to impede the movement of intramembrane particles across them. In aggregate these studies show that CD-induced perturbation of the absorptive cell cytoskeleton results in production of a transepithelial shunt which is fully explained by a defect in the transjunctional pathway. Furthermore, substantial structural abnormalities in occluding junction structure accompany this response. Lastly, the abnormalities in occluding junction structure and function coincide with structural changes in and contraction of the peri-junctional actin-myosin ring. These data suggest that a functionally relevant association may exist between the cytoskeleton and the occluding junction of absorptive cells. We speculate that such an association may serve as a mechanism by which absorptive cells regulate paracellular transport.

Regulatory role of calcium on histamine secretion

Calcium seems to have two opposing effects on histamine secretion from mast cells. A rise in the cytosol calcium concentration initiates the chain of reactions leading to histamine secretion. On the other hand, calcium appears to have a regulatory role, limiting the secretion. Removal of cell surface calcium enhances histamine secretion. The present work demonstrates an inhibitory effect of calcium in the medium, using low concentrations of compound 48/80 as the secretagogue. Histamine secretion in response to compound 48/80 primarily utilizes intracellular calcium. When low concentrations of compound 48/80 were used (usually 20-50 ng/ml), calcium (1 mM) inhibited the secretion, the inhibition being more pronounced as the pH was increased from 6.5 to 8.5. The higher pH conceivably promotes the binding of calcium to the phospholipids in the cell membrane. Calcium at this site seems to depress the efflux of calcium from the intracellular stores to the cytosol. The possibility that the removal of calcium from the cell surface causes increased sodium permeability was considered. However, the sodium channel blocker tetrodotoxin (10(-5) M) was equally ineffective in influencing histamine release in the presence and absence of calcium, indicating that a change of sodium permeability was not involved. Antigen-induced (anaphylactic) histamine secretion depends mainly on extracellular calcium, although some secretion occurs in a calcium-free medium. Addition of calcium alone to the medium caused only slight increase in the secretion, but when both phosphatidylserine and calcium were added histamine secretion was remarkably stimulated, apparently through the effect of phosphatidylserine on calcium transport across the plasma membrane.

Inhibition by amiloride of both adenylate cyclase activity and the Na +/H + antiporter in fish erythrocytes

In fish erythrocytes isoproterol stimulates cellular accumulation of cyclic adenosine 3′:5′-monophosphate (cyclic AMP) and produces a large increase in sodium permeability which corresponds to the activation of Na +/H + exchanges and chloride-dependent sodium uptake. The stimulation of sodium transport by isoproterenol was reproduced by adding cyclic AMP or forskolin to the medium and was blocked by propranolol. This increase in sodium permeability was completely inhibited by amiloride at the relatively high levels (0.1–1 mM) of the diuretic required to inhibit the activity of the Na +/H + exchanger under physiological conditions in various biological systems. It was shown that amiloride inhibited cyclic AMP accumulation. This effect, which was reversible and dose-dependent (ED 50 6 × 10 −6 M-maximal effect 0.5 mM), resulted from the inhibition of the catalytic unit of adenylate cyclase. Amiloride also directly inhibited the sodium entry system but the Na transporter was less sensitive than adenylate cyclase to amiloride (ED 50 6 × 10 −5 M). It appears from the data presented in this report that the inhibition of sodium permeability observed in fish erythrocytes in the presence of amiloride can result either from the effect of the diuretic on the adenylate cyclase system or from the effect on the sodium transport system, depending on the conditions in which amiloride is used. Thus, caution is required when interpreting amiloride action in terms of inhibition of specific transport processes.

Functional evidence for increased sodium permeability in aortas from DOCA hypertensive rats.

We studied the role of increased Na+ permeability on the increased responsiveness to ouabain and to K+-free solution in aortas from DOCA hypertensive rats. Helically cut strips from DOCA hypertensive and normotensive control rats were mounted in a muscle bath for recording isometric force. In response to ouabain, aortas from DOCA hypertensive rats were significantly more sensitive and developed a greater maximal force than aortas from control rats. The rate of force development in response to K+-free solution was significantly faster in aortas from DOCA hypertensive rats as compared to those from control rats. Monensin (10(-5)M), a Na+ ionophore, increased the contractile response to ouabain and the rate of force development in response to K+-free solution in both DOCA hypertensive and control aortas. Amiloride (3 X 10(-5) M), a Na+ channel blocker, decreased the contractile response to ouabain and the rate of force development to a K+-free solution in both the DOCA hypertensive and control aortas, but the magnitude of decrease was greater in aortas from DOCA hypertensive rats. Thus, a Na+ ionophore causes the control aortas to perform like those from DOCA hypertensive rats, and a Na+ channel blocker causes aortas from DOCA hypertensive rats to perform like those from control rats. It is concluded that the difference between the two is that the smooth muscle of aortas from DOCA hypertensive rats is more permeable to Na+ than is that from control rats.

Pregnancy induced hypertension: evidence for increased cell membrane permeability to sodium.

In a cross sectional study of 137 women of childbearing age (16-40) the effects of normal pregnancy, hypertensive pregnancy, and oral contraceptives on red cell electrolyte content and sodium efflux rates were examined and the results compared with values in a control group of normotensive, non-pregnant women. Efflux rate constants were significantly increased in normotensive pregnancy and in women taking oral contraceptives. This was associated with a significant increase in sodium permeability in the contraceptive group. A much larger increase in sodium permeability and efflux rate constant was seen in the hypertensive group. The results permit a hypothesis that the hormonal changes induced by pregnancy and oral contraceptives increase membrane permeability to sodium and stimulate sodium efflux. The rise in blood pressure associated with use of oral contraceptives may have a similar aetiology to that occurring in pregnancy induced hypertension.